Transplantable reticulum cell sarcomas (RCS) of SJL mice fail to grow in immunocompromised, syngeneic recipients and induce marked proliferation of Lyt-1+, 2- host T cells, without the development of RCS-specific cytotoxic cells. These phenomena appear to be under strict I-region gene control. Additionally, whereas normal SJL mice are classified as a "low" natural killer cell (NK) strain, lymphoid tissues from SJL mice bearing spontaneous, primary RCS or transplantable RCS lines exhibit high levels of NK activity. Previous studies have suggested that the major part of this NK activity is mediated by the tumor cells themselves. Thus, this may represent a unique mechanism by which tumor cells circumvent and/or overcome immune rejection. Given the apparent pre-B cell nature of RCS tumors (Thy-1-, sIg-, Ia+, Lyt-2+), it is critical to unequivocally demonstrate their NK-like and\-associated (i.e., interferon production) functions. This will be achieved in these studies by specifically isolating cells with NK cytolytic potential from tumorous lymphoid tissue and correlating their cytotoxic function with other characteristic properties of RCS cells: (1)\progressive tumor growth, (2)\expression of RCS surface determinants, (3)\capacity to stimulate syngeneic T cells and (4)\homing properties to B-cell areas of lymph nodes. The host component of the observed, RCS-associated NK activity will also be further characterized. Using lymphocyte growth factors and hybridization methodology, in vitro cell lines of RCS tumor cells and of the responding host T cells that they stimulate will be produced. Analysis of such cloned cell lines will be invaluable in addressing many of the questions regarding cell lineage, surface phenotype and functional properties, as well as target-receptor specificity of the cellular participants in RCS-associated NK activity. Since this murine lymphoma exhibits many similarities to some B-cell malignancies in humans, these studies may reveal significant host-tumor interactions that can be of potential benefit in the diagnosis and treatment of human disease.